Phosphorylated aminosugars: Synthesis, properties, and reactivity in enzymatic reactions
- Univ. of Wisconsin, Madison (United States)
A number of phosphorylated aminosugars have been prepared and tested as substrates for metabolic reactions. 6-Aminoglucose is a slow substrate for yeast hexokinase with a V{sub max} that is only 0.012% that of glucose. While V{sub max} is pH independent, V/K decreases below the pK of 9.0 of the amino group. 6-Aminoglucose is a competitive inhibitor vs glucose with a K{sub i} value increasing below the pK of 9 but leveling off at 33 mM below pH 7.16. Thus, protonation decreases binding affinity by 2.4 kcal/mol and only the neutral amine is catalytically competent. 6-Aminoglucose-6-P was synthesized enzymatically with hexokinase. Its pK's determined by {sup 31}P NMR were 2.46 and 8.02 ({alpha} anomer) and 2.34 and 7.85 ({beta} anomer), with a {beta}:{alpha} ratio of 3.0. It is most stable at pH 12, while as a monoanion its half-life is 3 h. The {sup 31}P NMR chemical shifts of the analogues are 8-8.5 ppm at pH 9.5. Their relative stability is 6-aminogluconate-6-P > 3-aminoglyceraldehyde-3-P > 6-aminoglucose-6-P > 6-aminofructose-1,6-bis-P{approx equal}6-aminofructose-6-P > 5-aminoribulose-5-P. These analogues were tested as substrates for their respective enzymes. Phosphorylated aminosugars are thus excellent isosteric analogues of normal metabolic intermediates, except for reactions catalyzed by kinases.
- OSTI ID:
- 5046843
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:20; ISSN 0006-2960; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
BARYONS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
CARBOHYDRATES
CHEMICAL REACTIONS
ELEMENTARY PARTICLES
ESTERS
FERMIONS
GLUCOSE
HADRONS
HEXOSES
ISOTOPES
KETONES
KINETICS
LIGHT NUCLEI
MAGNETIC RESONANCE
MONOSACCHARIDES
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEONS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PENTOSES
PHOSPHORIC ACID ESTERS
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
PHOSPHORYLATION
PROTONS
REACTION INTERMEDIATES
REACTION KINETICS
RESONANCE
RIBULOSE
SACCHARIDES
STABLE ISOTOPES
SYNTHESIS